Mirtazapine: Difference between revisions

'''Mirtazapine''' (trade names '''Remeron''', '''Avanza''', '''Zispin''' and many others) is a [[Chemical class::tetracyclic|tetracyclic antidepressant]] that, at higher doses, produces atypical [[Psychoactive class::psychedelic]], [[Psychoactive class::deliriant]], and [[sedative]] effects when [[administered]].

Mirtazapine was developed in the Netherlands and introduced in the United States in 1996.<ref> "REMERON (mirtazapine) tablet, film coated [Organon Pharmaceuticals USA]". DailyMed. Organon Pharmaceuticals USA. October 2012. Retrieved 24 October 2013.</ref> Its patent expired in 2004 and generic versions have been widely available since.<ref>Schatzberg, AF; Cole, JO; DeBattista, C. "3". Manual of Clinical Psychopharmacology (7th ed.). Arlington, VA: American Psychiatric Publishing.</ref>

Mirtazapine is broadly classified as an [[adrenergic]] and [[serotonergic]] [[antagonist]], and also has strong effects as an [[antihistamine]].<ref>Schatzberg, AF; Cole, JO; DeBattista, C. "3". Manual of Clinical Psychopharmacology (7th ed.). Arlington, VA: American Psychiatric Publishing.</ref>

 

Mirtazapine is used primarily in the treatment of major depressive disorder and other mood disorders.<ref>Mirtazapine: clinical overview. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/10446735</ref><ref>Review of the use of mirtazapine in the treatment of depression | http://informahealthcare.com/doi/abs/10.1517/14656566.2011.585459</ref> However, it has also been found useful in alleviating the following conditions and may be prescribed off-label for the treatment of

itching,<ref>Itch: scratching more than the surface | http://qjmed.oxfordjournals.org/content/96/1/7</ref><ref>Itch in systemic disease: therapeutic options | http://onlinelibrary.wiley.com/doi/10.1111/j.1529-8019.2005.00036.x/abstract</ref>and headaches and migraines.<ref>Mirtazapine Relieves Post-Electroconvulsive Therapy Headaches and Nausea: A Case Series and Review of the Literature | http://journals.lww.com/ectjournal/pages/articleviewer.aspx?year=2011&issue=06000&article=00016&type=abstract</ref><ref>Therapy of primary headaches: the role of antidepressants | http://link.springer.com/article/10.1007%2Fs10072-004-0280-x</ref><ref>[Effects of mirtazapine in patients with chronic tension-type headache. Literature review]. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17073214</ref>

Mirtazapine is a tertrahedric molecule of the piperazino-azepine and [[phenethylamine]] group of compounds. It is comprised of a fusion of pyridine, benzene, azepine, and piperazine rings. Mirtazapine is a tetracyclic antidepressant, named so because of their four-ring structure.  

Mirtazapine is the 6-aza analog of mianserin, which is pharmacologically similar in function.

Mirtazapine acts as an [[antagonist]]/inverse agonist upon the following receptors:<ref>Discovery of New Tetracyclic Tetrahydrofuran Derivatives as Potential Broad-Spectrum Psychotropic Agents | http://pubs.acs.org/doi/abs/10.1021/jm049632c</ref><ref>Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, org 3770 and its enantiomers (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/0028390888901499</ref>

*[[serotonin|5-HT_2A receptor]]<ref name="discovery">Fernández J, Alonso JM, Andrés JI, Cid JM, Díaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA. (2005)

J. Med. Chem., 48 (6): 1709-12. [PMID:15771415] </ref>

*5-HT_2B receptor<ref>The pharmacologic profile of mirtazapine. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8636062</ref>

*5-HT_2C receptor <ref name="discovery">Fernández J, Alonso JM, Andrés JI, Cid JM, Díaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA. (2005)

J. Med. Chem., 48 (6): 1709-12. [PMID:15771415] </ref>

*[[adrenaline|α₁-adrenergic receptor]]<ref>Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (in English) (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.</ref>

*α_2A-adrenergic receptor<ref>https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05345-3</ref>

*α_2B-adrenergic receptor<ref>Kennis LE, Bischoff FP, Mertens CJ, Love CJ, Van den Keybus FA, Pieters S, Braeken M, Megens AA, Leysen JE. (2000)

New 2-substituted 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine having highly active and potent central alpha 2-antagonistic activity as potential antidepressants.

Bioorg. Med. Chem. Lett., 10 (1): 71-4. [PMID:10636247] </ref>

*α_2C-adrenergic receptor<ref>https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05345-3</ref>

*H₁ receptor<ref>Synthesis and Pharmacological Testing of 1,2,3,4,10,14b-Hexahydro-6-methoxy-2-methyldibenzo[c,f]pyrazino[1,2-a]azepin and Its Enantiomers in Comparison with the Two Antidepressants Mianserin and Mirtazapine | http://pubs.acs.org/doi/abs/10.1021/jm010566d</ref>

*[[acetylcholine|mACH receptors]]<ref>Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (in English) (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8</ref>

While mirtazapine has some affinity for the 5-HT_2A receptor, it acts as an [[antagonist]]<ref> A Review of the Pharmacological and Clinical Profile of Mirtazapine http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2001.tb00198.x/epdf </ref> thus it is unlikely that this mechanism is responsible for its [[psychedelic]] and [[deliriant]] effects.

Mirtazapine has also been found to modulate the κ₃ opioid receptor, supporting the claim that mirtazapine causes pain relief<ref>Dapoigny M, Abitbol JL, Fraitag B. (1995)

Efficacy of peripheral kappa agonist fedotozine versus placebo in treatment of irritable bowel syndrome. A multicenter dose-response study.

Dig Dis Sci, 40: 2244-2249. [PMID:7587797] </ref> and adds to the [[sedative]] and [[hallucinogenic]] effects of mirtazapine<ref>Pande AC, Pyke RE, Greiner M, Wideman GL, Benjamin R, Pierce MW. (1996)

Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain.

Clin Neuropharmacol, 19: 451-456. [PMID:8889289]</ref><ref>Rimoy GH, Wright DM, Bhaskar NK, Rubin PC. (1994)

The cardiovascular and central nervous system effects in the human of U-62066E. A selective opioid receptor agonist.

Eur J Clin Pharmacol, 46: 203-207. [PMID:8070500] </ref>. This even may explain mirtazapine's withdrawal/discontinuation effects as well as its promotion of diurensis and a possible increase in food intake (usually resulting in weight gain).

It should be noted that although some of these effects are observed in those who take mirtazapine recreationally (or one off dosing) most neurophysiological effects are observed in those with on-going use (15, 30 and 45mg daily prescribed for depression, etc) due to a maintained level of mirtazapine in the body.

The mental processes, thought patterns and general head space experienced during a high dose mirtazapine experience is one that is typically described to be completely devoid of insight. In contrast to many other substances with hallucinogenic properties, it produces no [[introspection]], [[personal bias suppression|personal problem solving]] or [[creativity enhancement|creativity enhancing]] effects; for this reason it is generally reported that mirtazapine holds absolutely no therapeutic potential when used as a [[hallucinogen]].  

*'''[[Effect::Tactile hallucination]]''' - Unique tactile hallucinations are commonly felt within this substance. These can be described as bizarrely structured vibrations and pulsations that spontaneously manifest themselves across the skin.

*'''[[Effect::Restless legs]]'''

*'''[[Effect::Cognitive euphoria]]''' - Some reports of recreational mirtazapine use describe mild euphoria.

*'''[[Effect::Dream potentiation]]'''

*'''[[Effect::Emotion suppression]]''' - On mirtazapine, like other anti-depressants, emotions are dulled, and it is typically difficult to express them.

*'''[[Anxiety suppression]]''' - This effect is much stronger and more rapidly acting than that of SSRIs.

*'''[[Effect::Internal hallucination]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::scenarios and plots]]'') - The internal hallucinations which mirtazapine induces are generally only present as spontaneous breakthroughs at extremely high dosages as one is falling asleep. This effect's [[Internal_hallucinations#Variations|variations]] are delirious in believability, interactive in style, new experiences in content, autonomous in controllability and solid in appearance. The most common way in which they manifest themselves are through [[hypnagogic]] scenarios which the user may experience as they are drifting off to sleep. These are short and fleeting but frequent and completely believable and convincing as they happen. In terms of the theme they often take the form of bizarre and extremely nonsensical plots. These can also be observed in [[hypnopompic]] states (when one is waking from sleep).

===Combinational effects===

* [https://www.erowid.org/experiences/subs/exp_Pharms_Mirtazapine.shtml Erowid Experience Vaults: Mirtazapine]

Mirtazapine is considered to be relatively safe in the event of an [[overdose]],<ref name="Maudsley"/> although it is considered slightly more toxic in overdose than most of the SSRIs (except [[citalopram]]).<ref>{{cite journal | vauthors = White N, Litovitz T, Clancy C | title = Suicidal antidepressant overdoses: a comparative analysis by antidepressant type | journal = Journal of Medical Toxicology | volume = 4 | issue = 4 | pages = 238–50 | date = December 2008 | pmid = 19031375 | pmc = 3550116 | doi = 10.1007/bf03161207 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550116/pdf/13181_2009_Article_BF03161207.pdf | format = PDF }}</ref> Unlike the TCAs, mirtazapine showed no significant cardiovascular adverse effects at 7 to 22 times the maximum recommended dose.<ref name="pmid10333982"/> Case reports of overdose with as much as 30 to 50 times the standard dose described the drug as relatively nontoxic, compared to TCAs.<ref name="pmid9807651">{{cite journal | vauthors = Holzbach R, Jahn H, Pajonk FG, Mähne C | title = Suicide attempts with mirtazapine overdose without complications | journal = Biological Psychiatry | volume = 44 | issue = 9 | pages = 925–6 | date = November 1998 | pmid = 9807651 | doi = 10.1016/S0006-3223(98)00081-X }}{{Unreliable medical source|date=October 2011}}</ref><ref name="pmid9861579">{{cite journal | vauthors = Retz W, Maier S, Maris F, Rösler M | title = Non-fatal mirtazapine overdose | journal = International Clinical Psychopharmacology | volume = 13 | issue = 6 | pages = 277–9 | date = November 1998 | pmid = 9861579 | doi = 10.1097/00004850-199811000-00007 }}{{Unreliable medical source|date=October 2011}}</ref>

===Tolerance and addiction potential===

Tolerance to the effects of mirtazapine are built [[Time to full tolerance::almost immediately after ingestion]]. After that, it takes about [[Time to half tolerance::3 days]] for the tolerance to be reduced to half and [[Time to zero tolerance::7 days]] to be back at baseline (in the absence of further consumption). Mirtazapine presents cross-tolerance with [[Cross-tolerance::all [[psychedelic]]s]], meaning that after the consumption of mirtazapine all psychedelics will have a reduced effect.

 

*'''Other antidepressants''' - Different types of antidepressants can cause adverse effects as well as possible [[serotonin syndrome]] when mixed.

*'''United Kingdom''' - This substance is a licensed prescription-only medicine (POM) in the United Kingdom.<ref>{{cite web |url = http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con2025201.pdf|title = MHRA license for Modafinil in UK|date = November 10, 2006|author = MHRA|publisher = MHRA}}</ref> It is not a criminal offence to possess this medicine without a valid prescription. This medicine can legally be obtained with a valid prescription or through legal import of the medicine for personal use as outlined in Section 13 of the Medicines Act 1968.<ref>{{cite web |url = http://www.legislation.gov.uk/ukpga/1968/67/section/13|title = Medicines Act 1968 Section 13}}</ref>

===Community===

[[Category:Psychoactive substance]]

[[Category:Hallucinogen]]

[[Category:Psychedelic]]